The speed with which the COVID-19 vaccines were brought to fruition is possibly one of the greatest achievements in biopharmaceutical history. United by a common goal, unprecedented global collaboration driven by innovative technologies has proved what the industry is capable of and has catalyzed progress across the biopharmaceutical industry. In a recent e-book by The Medicine Maker and Pall ­­­­– Seeking Solutions in Biopharma– experts come together to reflect on the pandemic response and how it has spurred changes in the biopharmaceutical manufacturing paradigm with the goal of helping drug developers move more easily and quickly through different stages from discovery to manufacturing.

Separated into six parts, the e-book takes a look at the COVID-19 vaccine development and how the pandemic has re-shaped the biopharma manufacturing industry from the perspective of experts within Pall, across a number of areas of expertise.

Built for Change

In Built for Change, Morgan Norris, Vice President of Marketing at Pall, discusses viral vector production capacity and how the upward trajectory and challenges mirror what was experienced with monoclonal antibodies (mAbs) several decades ago. Viral vectors are the backbone of gene therapies that work either by introducing new genes to treat disease, replacing defective genes or silencing genes that cause disease. A bottleneck in manufacturing capacity and limited viral vector supply has hampered the pace of gene therapy development.

Norris believes that improvements to address low process yields, high cost of goods, and suboptimal unit operations will come swiftly. This is partly because of lessons learned from mAbs, but also because we are in the midst of a digital revolution poised to accelerate key tasks and facilitate efficient and global roll-out of new methodologies. Companies must be ready and willing to accept and adapt to these new paradigms.

Norris speaks of strategic corporate and infrastructure changes that will enable Pall to meet the changing tides of the industry beyond just creating the next great piece of technology. An end-to-end holistic approach in a rapidly evolving industry will better serve customers at every stage of development, whether it is ensuring supply chain security, easing tech transfer, or providing validation documents that are easily accessible through web portals.

Transforming Scientists into Drug Developers

The Danaher Life Sciences group, whose portfolio includes Pall, Cytiva and now Precision NanoSystems, provides the industry with truly comprehensive, end-to-end drug development and manufacturing solutions needed to help companies move forward with their drug candidates faster than ever before. In this article, Clive Glover, General Manager of Gene Therapy at Pall, and James Taylor, co-founder and General Manager of Precision Nanosystems, come together to discuss the origins of Precision Nanosystems and how its lipid nanoparticle platform marries Pall and Cytiva’s portfolios to expand the genomic medicine toolbox.

Messenger RNA (mRNA) therapeutics have been in development for many years, but the COVID-19 vaccines have brought the technology to the forefront and shone a light on its incredible potential to be used in the treatment of many different diseases. Lipid nanoparticle carriers have been integral to the success of both the approved mRNA vaccines, and has proved the clinical efficacy of this non-viral delivery mechanism that will help usher in a new era of genomic medicine. Glover emphasizes that mRNA delivery has always been a challenge and Precision NanoSystems has been a pioneer in this arena with its manufacturing technologies, delivery technologies, and the biological expertise in lipid nanoparticle delivery.

The effective partnership of Pall, Cytiva, and Precision Nanosystems is poised to provide the industry with truly comprehensive, end-to-end drug development and manufacturing solutions to meet the diverse needs of the industry across many disease indications. Taylor believes that the industry has reached a tipping point where the adoption of these technologies by the broader scientific community will drive an acceleration of innovation in medicine.

To Action Against COVID-19!

In this next article, To Action Against COVID-19!, Kevin Thompson, Technical Director, Process Engineering Project Management Group at Pall, recounts Pall’s involvement in the development, scale-up and manufacturing of the University of Oxford/AstraZeneca COVID-19 vaccine (brand names Vaxzevira and COVISHIELD).

Kevin discusses the process of engineering the hardware and consumables needed to produce the vaccine at large scale, based on the needs of the process development scientists, that was successfully rolled out to AstraZeneca and contract manufacturers in just 8 short weeks. One of the ways that Pall was able to deliver a vaccine manufacturing process in such a short timeframe was by leveraging its suite of standardized single-use equipment and consumables. These gave flexibility across different platforms that could be rapidly deployed, and have an extremely efficient supply chain. Additionally, many of the normal development and scale-up steps were either done in parallel, condensed or eliminated altogether (where possible) to expedite timelines. Through it all, collaboration and communication between stakeholders, within and external to Pall, were cited as critical elements to success.

The True Spirit of Collaboration

Benben Song, Global Product Manager, Technical Services at Pall, takes a look at the customer’s journey to commercialization especially in a complex environment like gene therapy. Song explains how companies do not need to embark on the journey alone. ­­­­­Leveraging experienced manufacturing partners with a deep understanding of process development, scale-up, and regulatory requirements, can provide support and insight for a project right from the start can pave the way for success. Song highlights some examples of the type of process development support services Pall provides to gene therapy customers as the sector continues to grow, from digital modeling services to onsite and/or virtual visits to review and optimize manufacturing protocols.

Winning the Long Race

In Winning the Long Race, Ruta Waghmare, Vice President, Scientific Affairs and Laboratory Services at Pall, and Deen Harman, Vice President of Pall’s biotech operations, provide insight into some of the factors they feel are needed to ensure long-term manufacturing success beyond establishing a suitable process.

According to Waghmare, scalability of a given process is an important consideration since demand for a therapeutic can change throughout different phases of a product’s lifecycle.  She advises companies to involve their operations team from the start, utilizing their experience and insight to develop a process that is as robust and scalable as possible to mitigate the incursion of additional challenges and costs.

Biopharma, along with many other industries, faced the harsh realities of global supply chain disruptions as a result of the COVID-19 pandemic. Companies like Pall are expanding supply chain capacity and ensuring redundancy, which Harman says now sits at around 20 times what it was before the pandemic. Additionally, strengthening strategic sourcing capabilities and securing relationships with vendors will allow Pall to be more adaptive to unforeseen changes in the future.

Converting Customer Need into Speed

Renaud Balsse, Biotech Integrated Solutions Manager at Pall, takes stock of the competitive gene therapy market as companies recognize the opportunities to deliver new therapeutics to patients. Balsse believes that developers need flexible, integrated solutions that bring disparate processes into a single coordinated, and controlled environment. Pall’s diverse portfolio of established, scalable single-use and hybrid platforms along with the engineering, process development and state-of-the-art modeling software, is suited to help developers overcome manufacturing pain points. With locations across the US, EU, and Asia, Pall’s Global Centers of Excellence are available to make sure that regulatory and customer expectations are not only met – but exceeded.

Seeking Continuous Improvement

As Waghmare and Harman alluded to in the Winning the Long Race chapter, manufacturing processes must adapt and evolve with the needs of the market, and opportunities for improvement should be undertaken to improve cost of goods, improve facility usage and more. In Seeking Continuous Improvement, Marc Bisschops, Senior Director, SLS – Integrated Process Solutions at Pall, makes a case for developers to considering continuous bioprocessing for faster, more efficient routes to market.

Continuous bioprocessing is part of process intensification, which aims to improve productivity to achieve higher titers. Bisschops speaks of analogies with mAbs where process intensification has increased titers by 100X what they were 20 years ago. Similar strategies should be undertaken to support the gene therapy industry as it matures to support demand and allow for flexibility to explore new therapeutic avenues. One key area that will be essential to adoption of continuous strategies will be better utilization of the digital space, from data management to digital twins and virtual reality platforms to remote operational control. As Bisschops emphasizes, this change may seem daunting, but it is not an all or nothing scenario ­– continuous can be used to simplify certain processes to improve the overall workflow. Proving the benefits of continuous with incremental changes will go a long way to alleviate the concerns of skeptics and those simply reticent to change. In the meantime, Pall will work with its customers to evaluate the risk profile of continuous and how to mitigate challenges to ensure confidence in their manufacturing process.

Pall and its partners in the Danaher Life Sciences portfolio are adapting to changes in the industry to support the growth and diversification in the gene therapy sector. Provision of flexible, integrated manufacturing solutions combined with end-to-end support from experts, enables drug developers to navigate the journey to commercialization faster and more efficiently than ever before. Lessons learned from the COVID-19 pandemic response has bolstered manufacturing capacity and has also informed investments into new scientific spaces that will allow Pall to remain agile to respond to the rapid pace of development and unforeseen future crises.

To download a copy of the e-book, please visit the link here: Seeking Solutions in Biopharma